Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

PLoS Negl Trop Dis. 2015 Sep 9;9(9):e0003950. doi: 10.1371/journal.pntd.0003950. eCollection 2015.

Abstract

This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Albendazole / administration & dosage*
  • Albendazole / pharmacokinetics
  • Animals
  • Anthelmintics / administration & dosage*
  • Anthelmintics / pharmacokinetics
  • Chitosan / administration & dosage*
  • Disease Models, Animal
  • Drug Carriers / administration & dosage*
  • Echinococcosis
  • Echinococcosis, Hepatic / drug therapy*
  • Echinococcus multilocularis / drug effects*
  • Histocytochemistry
  • Liver / parasitology
  • Liver / pathology
  • Male
  • Mice
  • Microspheres*
  • Plasma / chemistry
  • Treatment Outcome

Substances

  • Anthelmintics
  • Drug Carriers
  • Chitosan
  • Albendazole

Supplementary concepts

  • Alveolar echinococcosis

Grants and funding

This work was supported by the National Natural Science Foundation of China (NSFC nos. 81260412 and 81360453). The funders had no role in the study design, data collection and analysis, decision to publish and preparation of the manuscript process.